Our group is studying membrane protein structure and function by combining spectroscopic methods, such as fluorescence, with chemical, biochemical, immunochemical and molecular biological approaches. We are interested in the determining membrane protein structure and the origin of specific lipid-protein and protein-protein interactions. We have studied the relationship between amino acid sequence and structure using simple transmembrane helices. Such helices are the main structural element within membrane proteins. Their structure and location within the bilayer is analyzed using fluorescence, fluorescence quenching, circular dichroism and other spectroscopic techniques. These studies are allow us to derive basic rules for membrane protein folding and protein movement across membranes.

The Structure and Function of Cholesterol-Rich Membrane Domains

Together with Dr. Deborah Brown in the Dept. Of Biochemistry and Cell Biology we have been studying the structure and function of lipid domains enriched in cholesterol and sphingolipid. These domains have been proposed to have a functional role in processes such as viral and toxin entry into cells, protein sorting among organelles, signal transduction, prion formation and amyloid formation. Our studies involve determining the basic principles that drive the formation of these domains and regulate their lipid and protein composition. One project involves domains in bacteria, including (in collaboration with Dr. Jorge Benach, Dept. of Molecular Genetics and Microbiology) Borrelia burgdorferi, the bacterium that is the cause of Lyme disease. We are also carrying out studies on these domains in mammalian cells.

The principles of membrane domains formation can also be studied in artificial lipid vesicles. A limitation of using artificial membranes has been that they lack lipid asymmetry, the difference in lipid composition in their inner and outer layers found in many natural membranes. We have developed a method to prepare asymmetric artificial vesicles that closely mimic natural membrane, and are applying the methodology to analyze the rules for domain formation in natural membranes.